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Ischemic Heart Disease M M Elmazar BUE Ishemic heart disease 1 Definition: Ishemic heart disease Ischemic heart disease (IHD) is also known as coronary heart disease (CAD). It is the lack of oxygen and decreased or no blood flow to the myocardium resulting from coronary artery narrowing or obstruction. It may present in many different forms: eg. ACS (Acute coronary syndrome), AMI (Acute myocardial infarction) with ECG changes, STEMI or NSTEMI Chronic stable exertional angina or unstable angina Ischemia without symptoms Ischemia due to coronary artery vasospasm (variant or Prinzmetal’s angina) 2 Pathophysiology: Ishemic heart disease Major determinants of myocardial oxygen demand (MVo2) heart rate, contractility and intramyocardial wall tension during systole. A useful indirect estimate of MVo2 is the double product (DP) DP = HR X SBP (heart rate x systolic blood pressure) Prime determinants in occurrence of ischemia are: MVo2 and the caliber of resistance vessel delivering blood to the myocardium. The coronary system large epicardial vessel (R1) intramyocardial arterioles (R2) Normally, resistance in R2 > R1. Myocardial blood flow α coronary driving pressure α 1 / arteriolar resistance 3 Ishemic heart disease Atherosclerotic lesions occluding R1 increase arteriolar resistance, and R2 can vasodilate to maintain coronary blood flow. With greater degrees of obstruction, this response is inadequate and R2 vasodilation is insufficient to meet O2 demand Severe stenosis (>70%) stenosis (50 – 70%) - ischemia & symptoms at rest. - coronary reserve is diminshed due to vasoconstriction - obstruction is non consistent - reduces blood flow Abnormalities of ventricular contraction can occur resulting in heart failure, increased MVo2. 4 Clinical presentation: Ishemic heart disease Characteristics of angina pectoris include: sensation of pressure, tightness over the sternum or near to it Pain may radiate to the left arm, shoulder or other areas. Duration: between 30 seconds – 30 minutes. Precipitating factors: exercise, cold, anger, fright. Patients with Prinzmetal’s angina are more likely to experience pain at rest and in the early morning hours. Unstable angina is stratified into categories of low, intermediate or high risk for short-term death or non-fatal MI. Episodes of ischemia may also be painless or “silent” due to a higher threshold and tolerance for pain. 5 Diagnosis : Ishemic heart disease Important aspects of the clinical history: nature and duration of pain, precipitating factors, response to nitroglycerine,….. Existing personal risk factors for coronary heart disease: smoking, HT, DM A detailed family history should be obtained Physical examination including cardiac and noncardiac examinations (aortic aneurysms, peripheral vascular diseases) Laboratory tests eg. Hemoglobin, ECG, FBG, lipoprotein(a), Troponin T or I, myoglobin, CK-MB Exercise tolerance (stress) testing (ETT) is recommended Radionuclide angiocardiography (EF), ultrarapid computed tomography, echocardiography may be considered. 6 Desired outcome: Ishemic heart disease The goals of treatment to relieve the patient’s symptoms, maintain functional capacity, minimize adverse effects of treatment, and prevent progression to MI. Treatment: I) Modification of risk factors: Primary prevention by modification of risk factors will reduce the prevalence of IHD. Secondary intervention is effective in reducing morbidity and mortality. Risk factors are additive and can be classified as - alterable: smoking, HT, hyperlipidemia, stress, etc….. - unalterable: gender, age, (DM), etc…. 7 II) Pharmacologic Therapy: Ishemic heart disease a) B-Adrenergic Blocking Agents: Ideal candidates for B blockers include patients with chronic exertional stable angina, those with coexisting HT, supraventricular arrhythmias, angina and HF. B blockers are first line drugs in chronic angina. They can be used as monotherapy or in combination with Ca channel blockers and nitrates. If B blockers not tolerated or ineffective, then monotherapy with Ca channel blockers or combination therapy may be used. Initial doses of B blockers should be at the lower end of the usual dosing range and titrated to response. There is little evidence to suggest superiority of any particular B blocker..eg. propanolol Adverse effects: hypotension, bradycardia, bronchospasm…. Tapering of therapy over 2 days if it is to be discontinued to minimize withdrawal reactions. 8 B) Nitrates: Ishemic heart disease Action of nitrates: indirectly, through reduction of myocardial O2 demand 2ry to venodilation and directly, through dilation of coronary arteries and relief of spasm. Used to terminate an acute anginal attacks, prevent effort/stress induced attacks or for prophylaxis. Pharmacokinetic charecteristics : short half lives. eg. Nitroglycerin:1-5 min (exception isosorbide mononitrate half life 5 hours).First-pass effect of hepatic metabolism. Different dosage forms include: sublingual, buccal, spray, chewable and transdermal products. Adverse effects: postural hypotension, reflex tachycardia, headaches. A daily nitrate-free interval of 8-12 hours is necessary to prevent nitrate tolerance which is of quick onset and offset. Combination therapy is used in pts with more frequent symptoms ,or if B blockers / Ca channel blockers are ineffective or not tolerated. 9 C) Ca Channel blockers: Ishemic heart disease Actions: - vasodilation of systemic arterioles & coronary arteries. - depression of myocardial contractility and conduction velocity of AV and SV nodes. - decrease MVo2 - improve coronary blood flow in areas of obstruction. Eg. Verapamil and deltiazem, which cause less peripheral vasodilation than nifidepines but greater decreases in AV node conduction. Ideal candidates for Ca channel blockers include patients with contraindications or intolerance to B blockers, coexisting conduction system disease (excluding verapamil), severe ventricular dysfunction (best Amlodipine) 10 Ishemic heart disease Treatment of stable exertional angina pectoris: Regular exercise program should be undertaken improve C & M fitness. Nitrate therapy should be the first step in managing acute attacks of chronic stable angina if episodes are infrequent. (sublingual nitroglycerin tablets or sprays or buccal products) For prophylaxis when undertaking activities that lead to attacks, nitroglycerin sublingually or spray may be used. If angina occurs more frequently than once a day, chronic prophylactic therapy should be instituted. B adrenergic blocking agents are preferred esp. in patients with a fixed anginal threshold 11 Ishemic heart disease Ca channel antagonists can be used instead of B blockers for chronic prophylactic therapy . They are used in: patients with a variable threshold for exertional angina and pts with contraindications to B blockers. Verapamil not used in pts with conduction abnormalities and LV dysfunction, whereas amlodipine may be used. Deltiazem not be used in pts with pre-existing conduction disease or with other drugs with negative chronotropic effect. Nifidepine may cause excessive heart rate elevation and is best combined with B blocker. Chronic prophylactic therapy with long-acting forms of nitroglycerin may also be effective if angina occurs more than once daily. Monotherapy with nitrates should not be first line therapy unless B blockers and Ca channel blockers are contraindicated or not tolerated. 12 Chest pain -probability of coronary artery disease -high risk CAD unlikely Anti-anginal Drug treatment Education and risk factor Ishemic heart disease modification Initiate educational program Sublingual NTG History suggests vasospastic Angina? yes Side effect Or CI Aspirin if no contraindication Ca channel blocker, Long acting nitrate therapy Clopidogrel yes no Medications or conditions That provoke angina Treat yes appropriately yes Cigarette smoking Successful treatment yes Smoking Cessation program no no B-blocker therapy If no contradiction Yes Successful treatment Cholesterol high yes Add long acting Nitrate therapy If no CI yes Successful treatment yes no Serious Cont Ind Successful teatment see NCEP guidelines Blood Pressure yes high See JNC-VI guidelines no Serious Cont Ind no Add or substitute Ca channel yes Blocker if no Contraindication yes no Consider Revascularization therapy Routine follow up including Diet, exercise program, Diabetes management = treatment yes 13 Ishemic heart disease Treatment of unstable angina pectoris & NSTEMI: Immediate management involves risk stratification (Histroy, PhE, ECG, Biomarkers) to assign pts into one of the following categories (1) noncardiac diagnosis (2) chronic stable angina (3) possible ACS (4) definite ACS Anti-ischemic therapy for unstable angina includes: - bed rest with continuous monitoring for ischemia and arrhythmia - supplemental oxygen if cyanotic - immediate sublingual nitroglycerin followed by IV nitroglycerin - aspirin , heparin - IV B blockers followed by oral B blockers - if pain not relieved by nitrates: morphine sulphate IV. -ACE I should be given if hypertension or LV dysfunction persists after nitroglycerin and B blockers - long acting Ca channel blocker may be added if necessary or substituted for B blockers, if B blockers are contraindicated. 14 Ishemic heart disease Antithrombotic therapy is used based on the likelihood of ACS: - patients with possible ACS should receive only aspirin - patients with definite ACS should be treated initially with non-enteric coated aspirin followed by enteric coated aspirin and subcutaneous low molecular weight heparin (LMWH) (eg. Enoxaparin) or IV unfractionated heparin (UFH) - patients with definite ACS with continuing ischemia, other high risk factors or planned percutaneous coronary intervention (PCI) should receive aspirin plus LMWH or UFH and an IV platelet glycoprotein IIb/IIIa receptor antagonist ( eg. Abciximab) Patients intolerant to aspirin may receive clopidogrel, or ticlopidine. If PCI is planned , aspirin plus clopidogrel is used. Coronary angiography can be considered in certain cases. 15 Treatment of coronary artery spasm and variant angina pectoris: Ishemic heart disease Nitrates are the mainstay of therapy, mainly sublingual nitroglycerin or ISDN. IV nitroglycerin may be useful if patient not responding to sublingual preps. Calcium channel blockers may be considered as agents of choice because they are more effective, have fewer side effects, and can be given less frequently than nitrates. Combination therapy may be useful in unresponsive pts (nitrates+ Ca channel blockers) B blockers have no role as they may induce coronary vasospasm. Evaluation of therapeutic outcomes: Subjective and objective measures of drug response. Monitoring for major adverse effects should be undertaken. ECG, ETT can be used to evaluate response to therapy. Certain laboratory tests can be useful. 16